The synthesis of prostaglandins occurs in the eye. Aspirin-like compounds inhibit prostaglandin synthesis. A differential sensitivity of the prostaglandin synthetase system exists in different tissues. Arachidonic acid, a precursor of PGE2, elevates intraocular pressure and aqueous humor protein when applied topically. Aspirin-like compounds prevent the elevation of intraocular pressure and aqueous protein induced by arachidonic acid. Many ocular inflammatory responses may be mediated by prostaglandins. Uveitis and mechanical stimulation of the eye are associated with elevation of aqueous humor prostaglandin. Indomethacin or aspirin decreased the response of the eye to paracentesis, mechanical irritation, and compression. Thus, inhibition of prostaglandin synthesis may be effective in the treatment of a variety of ocular conditions and obviate the toxic side effects of corticosteroids. Many families of compounds inhibit prostaglandin synthesis such as the indole acetic acids, arylacetic acids, anthranilic acids, and pyrazolones. The present proposal is designed to study the effect of many inhibitors of prostaglandin synthesis, administered by a variety of routes, on the intraocular pressure and aqueous humor protein elevations induced by arachidonic acid in rabbits and monkeys. It will investigate the specificity of these blockers by testing their effects on non-prostaglandin mediated stimuli such as nitrogen mustard and formalin. The effects of the most potent compounds will be examined on experimental uveitis produced by intravitreal injections of bovine serum albumin. Hopefully, clinical therapeutic agents will be identified.